WO2022225802A1 - Sources d'ionisation par électronébulisation multiplexées utilisant une injection orthogonale dans un entonnoir d'ions électrodynamique - Google Patents

Sources d'ionisation par électronébulisation multiplexées utilisant une injection orthogonale dans un entonnoir d'ions électrodynamique Download PDF

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WO2022225802A1
WO2022225802A1 PCT/US2022/024973 US2022024973W WO2022225802A1 WO 2022225802 A1 WO2022225802 A1 WO 2022225802A1 US 2022024973 W US2022024973 W US 2022024973W WO 2022225802 A1 WO2022225802 A1 WO 2022225802A1
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vacuum chamber
ion
heated
inlets
ion beam
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PCT/US2022/024973
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English (en)
Inventor
Julia Laskin
Pei SU
Carlos LARRIBA
Xi Chen
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Purdue Research Foundation
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Priority to US18/287,357 priority Critical patent/US20240203720A1/en
Publication of WO2022225802A1 publication Critical patent/WO2022225802A1/fr

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    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/06—Electron- or ion-optical arrangements
    • H01J49/062—Ion guides
    • H01J49/065—Ion guides having stacked electrodes, e.g. ring stack, plate stack
    • H01J49/066—Ion funnels
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/04—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
    • H01J49/0468—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components with means for heating or cooling the sample
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/107—Arrangements for using several ion sources
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
    • H01J49/165—Electrospray ionisation

Definitions

  • the invention generally relates to systems and methods for multiplexed electrospray ionization.
  • Electrospray ionization is one of the most widely employed atmospheric pressure ionization techniques in mass spectrometry (MS).
  • MS mass spectrometry
  • ESI electrospray ionization
  • MS mass spectrometry
  • a high voltage is used to generate charged microdroplets from a liquid containing the analyte; the charged droplets undergo desolvation during which analyte ions are exposed and transferred into vacuum of a mass spectrometer.
  • ESI is widely employed both for analytical and preparative MS applications due to its simplicity and ease of operation, its soft ionization nature preventing ion fragmentation in the source, its exceptional compatibility with liquid-phase separation techniques, and its broad access to a wide range of molecules.
  • ESI is a promising ionization technique for producing high-intensity molecular ion beams for MS applications.
  • Bright ion sources are beneficial to analytical applications because they enhance the sensitivity and improve the duty cycle of mass spectrometers.
  • preparative MS using brighter ion sources improves the efficiency of surface and materials preparation using ions.
  • Early research on ion current improvement was focused on the efficient collection and transfer of ESI-generated ions into vacuum.
  • Specially-shaped heated capillary inlets have been employed to substantially increase the ion transmission at the atmosphere-vacuum interface of a mass spectrometer. Optimization of the inner diameter and length of the heated inlet results in an improved ion transmission.
  • Recent advancements include a space-charge-guided ambient ion beam merging using 3D-printed devices and arrayed emitters arranged in a circular pattern, which have substantially improved the overall signal and sensitivity of the instrument. Despite significant advances in this field, multiplexing of ion beams still results in substantial ion losses, which limit its analytical utility.
  • the invention provides systems and methods for multiplexing of ESI sources. Aspects of the invention include two or more heated inlets orthogonally injecting ions generated by separate ESI sources into an ion funnel. At least two heated inlets are located on the same side of the ion funnel while one or more additional inlets may be located on the opposite side. Such a layout can provide more than 3 -fold increase in total current compared to current generated from a single inlet and analytical performance can increase along with the increased total ion current. In certain embodiments, the total ion current produced may be approximately proportional to the number of inlets provided in the multiplexed apparatus.
  • the invention provides an apparatus for multiplexed electrospray ionization.
  • the apparatus may include a vacuum chamber, a plurality of ESI sources coupled to the vacuum chamber by a plurality of heated inlets.
  • the plurality of heated inlets can introduce ions to the vacuum chamber orthogonal to a direction of an ion beam within the vacuum chamber.
  • the two or more of the plurality of heated inlets can be located on the same side of the vacuum chamber and positioned such that each heated inlet introduces ions into the vacuum chamber at a point at least about 1 mm away from where another heated inlet introduces ions into the vacuum chamber.
  • the heated inlets may be positioned such that each heated inlet introduces ions into the vacuum chamber at a point at least about 2 mm away from where each other heated inlet introduces ions into the vacuum chamber, at least about 3 mm away from where each other heated inlet introduces ions into the vacuum chamber, at least about 4 mm away from where each other heated inlet introduces ions into the vacuum chamber, at least about 5 mm away from where each other heated inlet introduces ions into the vacuum chamber, or at least about 6 mm away from where each other heated inlet introduces ions into the vacuum chamber.
  • the heated inlets may be positioned at least 10 mm or at least 20 mm away from where each other heated inlet introduces ions into the vacuum chamber.
  • the vacuum chamber comprises an ion funnel.
  • the ion funnel may include a plurality of ring electrodes having a linearly decreasing inner diameter along the direction of the ion beam within the vacuum chamber.
  • the plurality of ring electrodes can have inner diameters that linearly decrease from about 50.8 mm to about 2.5 mm.
  • the vacuum chamber may comprise a repeller section upstream of the ion funnel along the direction of the ion beam within the vacuum chamber.
  • the plurality of inlets can introduce ions to the vacuum chamber at the repeller section.
  • the outlet of the vacuum chamber can be coupled to an inlet of a second vacuum chamber having a lower pressure than the vacuum chamber.
  • the second vacuum chamber can comprise a second ion funnel.
  • An outlet of the second vacuum chamber may be coupled to an inlet of a bent flatapole ion guide.
  • An outlet of the bent flatapole ion guide can direct the ion beam through a quadrupole mass filter to be focused by an einzel lens and directed onto a surface.
  • the surface can be a current collector plate.
  • the two or more of the plurality of heated inlets located on the same side of the vacuum chamber may be contained in a cartridge removably coupled to a first port in the side of the vacuum chamber. In certain embodiments, three or more of the plurality of heated inlets may be located on the same side of the vacuum chamber.
  • an apparatus of the invention may further comprise one or more additional electrospray ionization sources coupled to an opposite side of the vacuum chamber from the two or more of the plurality of heated inlets located on the same side of the vacuum chamber.
  • additional ESI sources may be coupled along the axis of the ion funnel.
  • the one or more additional electrospray ionization sources can be coupled to the opposite side of the vacuum chamber upstream or downstream of the vacuum chamber from the two or more of the plurality of heated inlets located on the same side of the vacuum chamber along the direction of the ion beam within the vacuum chamber. That arrangement can be termed a staggered layout.
  • a single heated inlet may be fed by two or more ESI emitters. Multiple heated inlets can then drive the ions into the vacuum chamber.
  • aspects of the invention include a method for focusing ions comprising the steps of: introducing ions into a vacuum chamber from a plurality of electrospray ionization sources independently coupled to the vacuum chamber by a plurality of heated inlets, wherein the plurality of heated inlets introduce the ions into the vacuum chamber orthogonal to a direction of an ion beam within the vacuum chamber, and wherein two or more of the plurality of heated inlets are located on a same side of the vacuum chamber; and focusing the ions in an ion beam at an outlet of the vacuum chamber.
  • the two or more inlets located on the same side of the vacuum chamber can be positioned such that each heated inlet introduces ions into the vacuum chamber at a point at least about 1 mm away from where another heated inlet introduces ions into the vacuum chamber.
  • Methods may further comprise directing the focused ion beam from the outlet of the vacuum chamber into an inlet of a second vacuum chamber having a lower pressure than the vacuum chamber.
  • methods may include further focusing the ion beam in the second ion funnel and directing the further focused ion beam from an outlet of the second vacuum chamber into an inlet of a bent flatapole ion guide. Additional steps may comprise cooling the ion beam in the bent flatapole ion guide, filtering the cooled ion beam in a quadrupole mass filter, and focusing the filtered ion beam with an einzel lens onto a surface.
  • FIG. 1 shows a prior art dual-polarity instrument for ion soft landing.
  • FIG. 2 panel A shows a drawing of an exemplary two-inlet cartridge used for multiplexing experiments.
  • FIG. 2 panel B shows a sectioned drawing of an exemplary ion funnel with two two-inlet cartridges implemented.
  • FIG. 2 panel C shows the front and top view of a complete drawing of an exemplary funnel implemented with four heated inlets.
  • FIG. 3 panel A shows IonCCD profiles of Ru(bpy)3 2+
  • FIG. 3 pane B shows the corresponding peak heights and SNRs for FIG. 3 a extracted from Lorentzian curve fitting.
  • FIG. 3 panel C shows shows IonCCD profiles of substance P.
  • FIG. 3 panel D shows the corresponding peak heights and SNRs for FIG. 3 c extracted from Lorentzian curve fitting.
  • FIG. 4 panel A shows mass-selected ion current of a few model cluster ions in ESIx 1 and ESIx4 mode.
  • FIG. 4 panel B shows mass-selected ion current of ubiquitin ions in ESIx 1 and ESIx4 mode.
  • FIG. 4 panel C shows mass-selected ion current of B12C1122- in ESIx2 mode using a different combination of inlets.
  • FIG. 4 panel D shows the stability of mass-selected ion current of B 120122- over an hour of time period.
  • FIG. 5 panel A shows ion current of Ru(bpy)3 2+ as a function of RF amplitude.
  • FIG. 5 panelB shows ion current of Ru(bpy) 3 2+ as a function DC gradient.
  • FIG. 5 panel C shows ion current of Ru(bpy) 3 2+ as a function pressure in the ion funnel.
  • FIG. 6 Top panel shows gas flow dynamics in the three-dimensional space of an exemplary HPF.
  • FIG. 7 shows a cross-section of an exemplary vacuum chamber having four heated orthogonal inlets directing ions into the vacuum chamber.
  • FIG. 8 shows an exemplary cartridge containing three heated inlets therein.
  • An electrodynamic ion funnel is commonly used on both commercial and custom- designed mass spectrometers.
  • An ion funnel is typically composed of a stack of ring electrodes applied with RF and DC voltages to efficiently focus and transmit ion beam in a wide pressure range (typically 0.1-30 Torr, up to atmospheric pressure).
  • ESI-generated ions are typically injected along the axial or orthogonal directions.
  • an orthogonally injected ion beam is delivered into the ion funnel through a heated inlet protruding into a cutout section on one side of the ion funnel. It has been shown that orthogonal injection has a better ion transmission compared to axial injection.
  • orthogonal injection decouples ion transfer from the gas flow dynamics, which efficiently eliminates the neutral contaminants and droplets entrained by the gas flow from the ion source.
  • a design of multiplexed ESI sources is reported using multiple orthogonal injections into an ion funnel.
  • a total of four orthogonal inlets are used for injection of ion beams into an ion funnel.
  • the two pairs of heated inlets are implemented on the opposite sides of the ion funnel with each of them equipped with an independently operated ESI emitter.
  • a more than 3-fold increase in total ion current was observed with four inlets as compared to the current generated from one inlet.
  • the analytical performance obtained using multiplexing improves in proportion with the total ion current. For a few model systems of different charge state and over a broad mass range, the total ion current produced using orthogonally multiplexed ESI source is almost proportional to the number of inlets.
  • a major obstacle in incorporating two or more inlets on the same side of the vacuum chamber is avoiding crosstalk or other negative effects caused by interactions between ions and neutral beams injected from the adjacent inlets. While the aforementioned 2x multiplex arrangements in the prior art such as depicted in FIG. 1 could avoid these issues, they were limited to a single inlet on each side rendering multiplexing at 3x or higher unfeasible.
  • the current invention has determined the proper spacing and angles required to avoid deleterious interactions of adjacent ion and neutral streams allowing for two, three, or more inlets to be included on each side.
  • the multiplexed ESI capability is implemented on a custom-designed dual polarity ion soft landing instrument described in detail elsewhere.
  • the instrument is composed of a high-transmission ESI interface (Spectroglyph, LLC) containing a tandem electrodynamic ion funnel system and a bent flatapole ion guide similar to the system shown in FIG. 1.
  • a high- pressure ion funnel (HPF) is housed in a vacuum chamber differentially pumped to 7 Torr by a dry screw vacuum pump (VARODRY VD200, 118 cubic feet per minute (cfm), Leybold GmbH, Cologne, Germany).
  • a low-pressure ion funnel is mounted in the second vacuum stage differentially pumped to 0.8 Torr by a multistage Roots vacuum pump (ECODRY 65 plus, 32 cubic feet per minute (cfm), Leybold GmbH, Cologne, Germany).
  • the third chamber which houses the bent flatapole ion guide is pumped down to 10-20 mTorr using a 90 L/s turbomolecular pump (TURBOVAC 90 I, Leybold GmbH, Cologne, Germany).
  • the fourth vacuum stage in which ion current detection and ion beam characterization are performed, is differentially pumped to 3-6 x 10 5 Torr by a 350 L/s turbomolecular pump (TURBOVAC 350 I, Leybold GmbH, Cologne, Germany).
  • the two turbomolecular pumps are backed by ECODRY 65 plus used for the second vacuum chamber.
  • FIG. 1 An earlier high-transmission ESI interface described in Su, P.; Hu, H.; Warneke, T; Belov, M. E.; Anderson, G. A.; Laskin, J. Design and Performance of a Dual -Polarity Instrument for Ion Soft Landing.
  • Anal. Chem. 2019, 91, 5904-5912 is depicted in FIG. 1 and is equipped with two orthogonal injection ESI sources. Ions are introduced into vacuum through stainless steel heated inlet tubes from the opposite sides of the HPF. Each inlet tube is mounted using a stainless-steel cartridge. The temperature of each heated inlet is maintained by a cartridge heater and a thermocouple.
  • the heated cartridges were modified to accommodate two inlets on each side of the HPF.
  • a detailed drawing of the cartridge is shown in FIG. 2a.
  • two heated inlets (1/16” OD, 0.04” ID, 7 cm length, VICI Valeo Instruments, Houston, TX) are inserted through the center of the cartridge and are spaced by 6 mm.
  • Two 24V 60W cartridge heaters (1/8” dia., 1-1/4” long, Gordo Sales, Layton, UT) are connected in series and inserted into the side channels of cartridge to provide enough heating power for efficient desolvation of the ESI droplets.
  • a thermocouple wire is inserted into the channel in between the heaters.
  • a cartridge may contain 2, 3, 4, 5, or more individual inlets to allow for a single vacuum chamber to be configured to multiplex various numbers of sources simply by swapping cartridges or by only using a few inlets within a cartridge.
  • FIG. 8 shows an exemplary cartridge having three inlets.
  • FIG. 7 shows an exemplary configuration in cross-section using a single inlet cartridge opposite a three- inlet cartridge to allow for multiplexing of up to four ion sources.
  • adjacent inlets should be positioned such that their outlet points where ions are introduced into the vacuum chamber (e.g., ion funnel) are spaced at least lmm apart.
  • the adjacent inlets may be spaced at least about 2, at least about 3, at least about 4, at least about 5, at least about 6 mm apart, at least 10 mm apart, at least 15 mm apart, at least 20 mm apart, at least 25 mm apart, or at least 30 mm apart.
  • An additional advantage of cartridges is the ability to tightly control the spacing and angles of each adjacent jet in order to avoid deleterious interactions therebetween. Accordingly, setup time when switching between cartridges and multiplex arrangements can be greatly reduced by maintaining a preset inlet spacing in each cartridge.
  • the HPF is specially designed for orthogonal injection inlets (FIG. 2b).
  • it is composed of a repeller section and a funnel-shaped section.
  • the repeller section is assembled using a stainless-steel plate with two slot windows and a stack of 28 ring electrodes with identical inner diameters of 50.8 mm (2 in).
  • Two cutouts (dimension) on the opposite side of the repeller section of the HPF are implemented for introducing the ion beam into the ion funnel.
  • the two cutouts are implemented at staggered locations along the axis of the HPF to improve the gas dynamics of the ion funnel.
  • one cutout is positioned between the 9 th and the 16 th ring electrodes, while the other one is positioned between the 14 th and the 21 st ring electrodes.
  • FIG. 2c shows a cross-sectional diagram of the funnel on the radial plane when the four orthogonal inlets are inserted into the funnel.
  • the funnel-shaped section of the HPF is composed of 85 ring electrodes with IDs decreasing linearly from 50.8 mm to 2.5 mm (0.1 in).
  • the last ring electrode acts as a conductance limit between the first and the second vacuum chambers.
  • Direct infusion ESI is used to generate ions in all the experiments discussed in this work.
  • a solution of a selected analyte ion is filled into a gastight syringe (Hamilton Robotics, Reno, NV) and introduced into the ESI source through a MicroTight union (P-720, IDEX Health & Science, Oak Harbor, WA) and a fused silica capillary (lOOpm ID, 360 pm OD, G length, Polymicro Technologies, Phoenix, A Z) using a syringe pump (Cole-Palmer, Vernon Hills, IL) at a typical flow rate of 60pL h 1 .
  • a gastight syringe Hamilton Robotics, Reno, NV
  • MicroTight union P-720, IDEX Health & Science, Oak Harbor, WA
  • a fused silica capillary lOOpm ID, 360 pm OD, G length, Polymicro Technologies, Phoenix, A Z
  • a syringe pump Cold-Palmer, Vernon Hills, IL
  • Suitable ion sources include atmospheric pressure chemical ionization (APCI), atmospheric Pressure Photoionization (APPI), desorption electrospray ionization (DESI), nano-DESI, matrix-assisted laser desorption/ionization (MALDI), laser ablation electrospray ionization (LAESI), and any other ambient ionization source.
  • APCI atmospheric pressure chemical ionization
  • APPI atmospheric Pressure Photoionization
  • DESI desorption electrospray ionization
  • MALDI matrix-assisted laser desorption/ionization
  • LAESI laser ablation electrospray ionization
  • Any other ambient ionization source Charged microdroplets are produced by applying a ⁇ 3 kV voltage to the stainless-steel syringe needle. The microdroplets are transferred into the ion funnel through a heated inlet where desolvation takes place to generate ions. In the multiplexed mode where more than one direct infusion capillary is used to generate
  • the capillaries used to introduce ions from the same side of the HPF are held by PEEK sleeves (F-388, IDEX Health & Science, Oak Harbor, WA) mounted on a 3D-printed bracket.
  • the bracket is mounted on a 3-axis Dovetail translation stage (DT12XYZ, Thorlabs Inc., Newton, NJ), which allows for the optimization of the position of the ESI capillaries with respect to the inlets.
  • the analytical performance of the multiplexed source is evaluated using a mass- dispersive device, rotating wall mass analyzer (RWMA) described in detail elsewhere.
  • RWMA rotating wall mass analyzer
  • ion beam transferred through the bent flatapole ion guide is directed into high vacuum and sent to the RWMA through an einzel lens.
  • Ions of different m/z are spatially dispersed into concentric rings of different radii by RWMA.
  • Ion beam after the RWMA is characterized using a position-sensitive IonCCD (01 Analytical, Pelham, AL) detector.
  • the ring- shaped ion beam is characterized by a pair of peaks symmetrically located around the center of the one-dimensional IonCCD profile.
  • Data acquisition using the IonCCD detector is performed by first acquiring a baseline profile during which the ion beam is switched off; in the following step, ion beam is switched on, and the ion beam profile is obtained by averaging 50 consecutive profiles each acquired at an integration time of 10 ms.
  • the intensity of a signal in the IonCCD profile is obtained using Lorentzian curve fitting from which the peak height is extracted.
  • the raw IonCCD profile is first fitted with a 3 rd order polynomial using a Savitzky-Golay filter embedded in OriginLab (Northampton, MA) with 50 points of window; next, the noise is extracted by calculating the standard deviation of the raw profile from the fitted profile.
  • Signal-to-noise ratio (SNR) is obtained by taking the ratio of the peak height and the noise.
  • Tris(2,2'-bipyridyl)dichlororuthenium(II) hexahydrate (Ru(bpy)3 ⁇ 6H2O, CAS: 50525-27-4), sodium phosphotungstate tribasic hydrate (Na3[PWi204o] H2O, CAS: 12026-98-1), substance P acetate salt hydrate (CAS: 137348-11-9, anhydrous), ubiquitin from bovine erythrocytes (>98% purity, CAS: 79856-22-4).
  • TSA 2Bi2Cli2 salt.
  • Na[V607(0CH3)i2] and [Co6S8(PEt3)6]Cl was synthesized according to reported procedures.
  • Other analytes were dissolved in methanol at a concentration of 150 pM unless specified otherwise.
  • RWMA rotating wall mass analyzer
  • ions of different m/z are dispersed onto ring shaped areas of distinct radii on a surface.
  • a position-sensitive IonCCD detector was used to characterize the ion beam.
  • a ring-shaped ion beam is detected as a pair of signals symmetrically located around the center of the one-dimensional IonCCD profile.
  • the multiplexing performance was evaluated using several model systems.
  • the pair of peaks in each profile was assigned to Ru(bpy)3 2+ as the dominant ionic species generated in the ESI source.
  • the peak height shown in FIG. 3b increases almost proportionally with the number of inlets in use, with a slightly lower increase from ESE3 to ESE4 mode.
  • SNR signal-to-noise ratio
  • ESU4 mode Using multiplexing in ESU4 mode, a 2.8-fold increase was obtained on average in the total ion current compared to the current generated using a single ESI emitter.
  • An LTQ mass spectrum of 5 mM ubiquitin in 49.5:49.5:1 methanol/FhO/CFECOOFl (v/v/v) shows a charge state distribution centered at 10+.
  • the same solution was used to test the multiplexing of ubiquitin ion beam in ESU4 mode. In ESU4 mode, a 3.1 -fold increase on average in ion current was observed for ubiquitin ions of charge states from 7+ to 13+. This confirms the applicability of multiplexing to a broad range of molecular ions.
  • FIG. 1 While the device shown in FIG. 1 allowed for multiplexing of the same ions by introducing two orthogonal injections from opposite sides of the ion funnel, systems and methods of the current invention allow for injection of independent ion beams from three, four, or more orthogonal inlets by introducing two of them on each side of the funnel.
  • the total ion current obtained in the ESU4 mode was higher than reported in previous work. It is hypothesized that the performance of multiplexing is independent of which of the inlets are used. To test the hypothesis, the ESU2 mode was operated in by introducing the two ion beams from the same and the opposite side of the ion funnel.
  • FIG. 1 While the device shown in FIG. 1 allowed for multiplexing of the same ions by introducing two orthogonal injections from opposite sides of the ion funnel, systems and methods of the current invention allow for injection of independent ion beams from three, four, or more orthogonal inlets by introducing two of them on each side of the funnel.
  • 4c shows the mass-selected ion current of B12CI12 2 obtained in the ESI> ⁇ 2 mode with different position of ion beam injection. Similar ion current was observed independent of which of the two inlets were used for ion beam injection. This proves that orthogonally-injected ion beam introduced from different positions of the ion funnel can be efficiently merged to create a brighter ion beam.
  • FIG. 4d show the mass-selected ion current of B12CI12 2 in ESIx4 mode, which was observed to be stable for at least an hour (FIG. 4d). This corresponds to a deposition rate of ⁇ 20 pg of mass-selected ions per day, which substantially improves the efficiency of ion deposition experiments.
  • the ion transmission efficiency of ion funnels strongly depends on the operating pressure and tuning parameters for ion topics.
  • the radiofrequency (RF) electric field facilitates the radial confinement of the ion cloud; meanwhile, the DC field promotes the ions to move to the downstream ion optics along the axis of the funnel.
  • RF radiofrequency
  • DC field promotes the ions to move to the downstream ion optics along the axis of the funnel.
  • Ru(bpy)3 2+ was selected as the model system; ion current was measured on the rods of the bent flatapole ion guide, which corresponds to the transmitted ion current through the tandem ion funnel system. It is noted that ESI of Ru(bpy)3Cl2 in methanol produces Ru(bpy) 3 2+ ions as the only dominant ionic species in positive ion mode. Although the ion current collection was performed before the mass-selection stage, these measurements provide direct insights into the transmission efficiency of ion funnel independent of the performance of the downstream ion optics when a high-intensity ion beam is transmitted. FIG.
  • 5a shows the ion current transmitted at different RF amplitudes at a resonance frequency of 740 kHz.
  • the transmission efficiency increased with increased RF level, and a plateau was reached at -230 V p-p.
  • Further increase in rf level resulted in a decrease in transmission, which may be attributed to the higher low-mass-cut-off at relatively high rf levels.
  • the optimal rf level found for ESG4 mode is substantially higher.
  • ESI> ⁇ 4 mode This may be atributed to the space charge effect from a stronger ion cloud in ESI> ⁇ 4 mode, which requires a deeper RF potential well to radially confine the ion beam.
  • gas dynamics in ESI> ⁇ 4 mode is expected to be distinctly different from ESI> ⁇ 2 mode when four stream of gas flows are introduced from the opposite side.
  • FIG. 5b shows the transmitted ion current at different DC gradients.
  • the HPF is composed of a repeller section and a funnel section as described in the experimental section.
  • the DC gradient in the repeller section did not play an important role in improving the ion transmission.
  • the ion current increases with a higher axial DC gradient in the funnel region.
  • the highest ion current was obtained at a DC of voltage 320 V. Further increasing the DC gradient caused a failure in the electronic power supply, which results in a substantially dropped unstable ion current (FIG. 5b, DC voltage at 330 V).
  • the effect of pressure on ion transmission was also studied and the results are shown in FIG. 5c.
  • the operating pressures in the ion funnel were adjusted by choking the valve on the VARODRY VD 200 mechanical pump.
  • the highest ion transmission was observed at the lowest pressure with the highest obtainable pumping power (7.25 Torr).
  • Increasing the pressure in the ion funnel results in proportionally decreased ion current. It is anticipated that the ion transmission may be further improved if more powerful pumps are employed.
  • FIG. 6a shows the gas flow dynamics in the three- dimensional space.
  • the repeller region where gas was introduced into the ion funnel shows the highest gas flow velocity, which manifests the supersonic gas expansion in vacuum.
  • the streams of gas flow from the opposite side of the ion funnel interact with each other and form a vortex gas flow with a relatively lower velocity.
  • the gas flow streams merge together in the funnel- shaped region and move towards the exit of the HPF, which facilitates the transmission of the ion beam. This is validated by the ion trajectory simulation in FIG. 5b and experimentally observed additive ion transmission from the four inlets in ESI> ⁇ 4 mode.

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Abstract

L'invention concerne de manière générale des systèmes et des procédés pour l'ionisation par électronébulisation multiplexée. Dans certains modes de réalisation, des sources d'ionisation par électronébulisation injectent orthogonalement des ions dans un entonnoir d'ions avec au moins deux des sources injectant sur le même côté de l'entonnoir d'ions.
PCT/US2022/024973 2021-04-20 2022-04-15 Sources d'ionisation par électronébulisation multiplexées utilisant une injection orthogonale dans un entonnoir d'ions électrodynamique WO2022225802A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130337456A1 (en) * 2007-04-13 2013-12-19 Sequenom, Inc. Comparative sequence analysis processes and systems
US20140291507A1 (en) * 2011-11-02 2014-10-02 Micromass Uk Limited Multi Inlet For Solvent Assisted Inlet Ionisation
US20180038829A1 (en) * 2011-10-27 2018-02-08 Beckman Coulter, Inc. Capillary electrophoresis-electrospray ionization-mass spectrometry system
US20200015717A1 (en) * 2018-07-12 2020-01-16 Trace Matters Scientific Llc Reconfigurable Sequentially-Packed Ion (Spion) Transfer Device and System

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130337456A1 (en) * 2007-04-13 2013-12-19 Sequenom, Inc. Comparative sequence analysis processes and systems
US20180038829A1 (en) * 2011-10-27 2018-02-08 Beckman Coulter, Inc. Capillary electrophoresis-electrospray ionization-mass spectrometry system
US20140291507A1 (en) * 2011-11-02 2014-10-02 Micromass Uk Limited Multi Inlet For Solvent Assisted Inlet Ionisation
US20200015717A1 (en) * 2018-07-12 2020-01-16 Trace Matters Scientific Llc Reconfigurable Sequentially-Packed Ion (Spion) Transfer Device and System

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SU ET AL.: "Design and Performance of a Dual-Polarity Instrument for Ion Soft Landing", ANAL. CHEM., vol. 91, no. 9, 19 April 2019 (2019-04-19), pages 5904 - 59121, XP055983274, Retrieved from the Internet <URL:https://pubs.acs.org/doi/abs/10.1021/acs.analchem.9b00309> *

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